Background The diagnosis of Mycobacterium tuberculosis infection increasingly relies on interferon‐gamma release assay (IGRA) technologies. Despite their usefulness, inconsistency in IFN‐ γ responses and the persistence of indeterminate results remain problematic across IGRA platforms. The present study aimed to comparatively assess three commercial IGRA assays (TBF‐ELISA, TBF‐FIA, and QFT‐Plus) with emphasis on IFN‐ γ production and factors influencing indeterminate results. Methods The study employed a cross‐sectional design and was implemented at the National Public Health and Reference Laboratory in Ghana. A total of 1148 individuals were enrolled consecutively and stratified according to their TB exposure status. Parallel testing of collected blood samples was performed with the three IGRA assays. IFN‐ γ production was quantified, and the rate of indeterminate results was analyzed. Multivariate regression analyses were performed to assess determinants of IFN‐ γ levels and indeterminate results. Results Significant quantitative differences in IFN‐ γ responses were observed across platforms ( p 1.5 IU/mL). Indeterminate rates differed significantly (TBF‐FIA 13%, QFT‐Plus 8%, TBF‐ELISA 6%; Cochran’s Q test, p < 0.001). Demographic factors were not associated with assay failure; however, sample collection sites were significantly related. Notably, healthcare workers and TB contacts showed lower IFN‐ γ responses than expected. Conclusion While all three IGRAs effectively differentiate TB infection status, the variability in IFN‐ γ responses and indeterminate rates is an indication that they may not be interchangeable. TBF‐FIA demonstrated the highest variability, requiring further investigation. The findings suggest that each test has its own strengths and limitations, thus, the need for selective use depending on the clinical setting and testing purpose.
Kutame et al. (Thu,) studied this question.